TAZ is required for the osteogenic and anti-adipogenic activities of kaempferol

Mi Ran Byun, Hana Jeong, Su Jung Bae, A. Rum Kim, Eun Sook Hwang, Jeong Ho Hong

Research output: Contribution to journalArticlepeer-review

70 Scopus citations

Abstract

Kaempferol (KMP) exerts protective effects against both osteoporosis and obesity by regulating cellular activities, but the underlying molecular mechanisms have not been fully elucidated. TAZ (transcriptional coactivator with PDZ-binding motif) modulates both osteoblast and adipocyte differentiation from mesenchymal stem cells by stimulating the activities of RUNX2 (runt-related transcription factor 2) and suppressing the activities of PPARγ (peroxisome proliferator-activated receptor γ). In this study, we investigated the effects of KMP on TAZ regulated osteoblast and adipocyte differentiation. KMP increased the osteoblast differentiation of mesenchymal cells by facilitating the physical interaction between TAZ and RUNX2, thus the increasing transcriptional activities of RUNX2. KMP also enhanced the association of TAZ with PPARγ, thereby suppressing the gene transcription of PPARγ targets and resulting in diminished adipocyte differentiation. Interestingly, the regulatory effects of kaempferol on RUNX2 and PPARγ-mediated transcriptional activity were impaired in TAZ-null mouse embryonic fibroblasts but recovered by restoration of TAZ expression. Our results demonstrate that KMP fortifies TAZ activity, which enhances RUNX2-mediated osteoblast differentiation and suppresses PPARγ-stimulated adipocyte differentiation, indicating the potential of KMP as an effective therapeutic reagent for controlling bone loss and adiposity through TAZ activation.

Original languageEnglish
Pages (from-to)364-372
Number of pages9
JournalBone
Volume50
Issue number1
DOIs
StatePublished - Jan 2012

Bibliographical note

Funding Information:
We thank Dr. Thomas Benjamin (Harvard University) for sharing TAZ KO MEF cells and the Aging Tissue Bank (Pusan National University) for kindly providing KMP. This work was supported by the Basic Science Research Program of the National Research Foundation of Korea ( 314-2008-1-E00283 , 2009–0084879 and 2009–0075911 ) and grant from Korea University .

Keywords

  • Adipocyte
  • Differentiation
  • Kaempferol
  • Osteoblast
  • TAZ

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